The research projects currently under way in this laboratory comprise a broad program designed to probe the role of class II MHC molecules in immunity and self-tolerance; in the failure of self-tolerance, and to develop means to potentiate or to block the action of MHC molecules in mediating the immune response to foreign antigens, self antigens and self-tumor antigens. The knowledge of structure-function relationships of MHC class II molecules gained in these experiments will then be applied to several animal disease models and human disease states. Parallel experiments are designed to determine the immuno-regulatory role of lymphokines, which directly or indirectly regulate the level of expression and site of expression of class II MHC molecules. A separate set of experiments will expand our on-going study of MHC class II allelic polymorphism by searching for class II polymorphic sequences in species which have diverged from the human evolutionary line five million years ago (chimpanzees) and approximately 20 million years ago (cynomolgus monkeys). These experiments should permit an evaluation of the evolutionary conservation of class II MHC polymorphic sequences critical for the function of these molecules in regulating the immune response.